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Determining whether a cancerous tumor originated in a given location or spread there from another tissue or organ in the body is important when assessing the likely course of a patient's disease. When the origin of the primary tumor cannot be identified, it can be challenging to properly diagnose the malignancy and determine the best treatment strategy.

Now, researchers at the University of California San Diego have identified a microbial DNA signature in blood plasma that reliably differentiates primary liver cancer from colorectal cancer that has spread to the liver (metastatic colorectal cancer). The study was published in eGastroenterology.

"The use of microbial DNA signatures could open up a new diagnostic pathway, especially in situations where radiographic imaging is ambiguous or not accessible, " said Amir Zarrinpar, MD, Ph.D., professor in the Division of Gastroenterology & Hepatology at UC San Diego School of Medicine.

The researchers isolated cell-free DNA (cfDNA)—fragments of DNA from dead cells that are found in bodily fluids—from the blood plasma of 16 patients diagnosed with primary liver cancer and 11 patients diagnosed with metastatic colorectal cancer.

A metagenomic analysis revealed that:

While larger studies are needed, the findings support growing evidence of microbial involvement in cancer biology.

"This is one of the first studies to show that microbial DNA in blood may be used to noninvasively distinguish tumor origin without the use of machine learning or artificial intelligence, particularly between two common liver pathologies, " said Zarrinpar.

The research has potential clinical applications including early cancer detection and monitoring of high-risk patients, and could contribute to the development of microbial DNA-based biomarkers for diagnosis and microbiome-based cancer therapies.

More information: eGastroenterology (2025). DOI: 10.1136/egastro-2025-100193